Nonribosomal peptides in fungal cell factories: from genome mining to optimized heterologous production

Vassaux, Antoine; Meunier, Loïc; Vandenbol, Micheline; Baurain, Denis; Fickers, Patrick; Jacques, Philippe; Leclère, Valérie

doi:10.1016/j.biotechadv.2019.107449

Cited by 28 publications

(14 citation statements)

References 237 publications

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“…We then set out to identify the putative biosynthetic pathway that was deduced to be of NRPS and PKS-based origin. 15–17 Mining of the obtained draft genome sequence using FungiSmash 18 revealed only one biosynthetic gene cluster (BGC) region, designated as the xya cluster ( Fig. 3 ; GenBank accession number MW579544), that encodes for a highly-reducing PKS (HRPKS) xyaA (KS-AT-DH-CMet-ER-KR), a bimodular nonribosomal peptide synthase (NRPS) xyaB (C 1 -A 1 -T 1 -E 1 -C 2 -A 2 -T 2 -C T ), a major-facilitator superfamily (MFS) transporter xyaC and two short-chain dehydrogenases/reductases (SDR) xyaD / xyaE .…”

Section: Resultsmentioning

confidence: 99%

“…We then set out to identify the putative biosynthetic pathway that was deduced to be of NRPS and PKS-based origin. [15][16][17] Mining of the obtained dra genome sequence using FungiSmash 18 revealed only one biosynthetic gene cluster (BGC) region, designated as the xya cluster (Fig. 3; GenBank accession number MW579544), that encodes for a highly- 13.5, q 0.89, dd (7.5, 7.5) 13.4, q 0.87, dd (7.5, 7. biosynthesis of the structurally related lipodepsipeptides valactamide A-H 20 (Fig.…”

Section: Biosynthesismentioning

confidence: 99%

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GNPS-guided discovery of xylacremolide C and D, evaluation of their putative biosynthetic origin and bioactivity studies of xylacremolide A and B

Schalk

Fricke

et al. 2021

RSC Adv.

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Section: Resultsmentioning

confidence: 99%

Section: Biosynthesismentioning

confidence: 99%

GNPS-guided discovery of xylacremolide C and D, evaluation of their putative biosynthetic origin and bioactivity studies of xylacremolide A and B

Schalk

Fricke

et al. 2021

RSC Adv.

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“…S. cerevisiae shows a high affinity of codon usage and a certain tolerance to exogenous bacterial sequences [ 104 ]. In addition, yeasts produce few endogenous SMs, minimizing competition of exogenous BGCs with cognate SM pathways and thus simplifying the detection and purification of target compounds [ 105 ]. The heterologous expression of BGCs from terrestrial bacteria and fungi has been proved workable in yeasts, while there have been few successful examples of BGCs from marine microorganisms expressed in yeasts.…”

Section: Heterologous Hosts For Mnpsmentioning

confidence: 99%

Recent Advances in the Heterologous Expression of Biosynthetic Gene Clusters for Marine Natural Products

et al. 2022

Marine Drugs

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Marine natural products (MNPs) are an important source of biologically active metabolites, particularly for therapeutic agent development after terrestrial plants and nonmarine microorganisms. Sequencing technologies have revealed that the number of biosynthetic gene clusters (BGCs) in marine microorganisms and the marine environment is much higher than expected. Unfortunately, the majority of them are silent or only weakly expressed under traditional laboratory culture conditions. Furthermore, the large proportion of marine microorganisms are either uncultivable or cannot be genetically manipulated. Efficient heterologous expression systems can activate cryptic BGCs and increase target compound yield, allowing researchers to explore more unknown MNPs. When developing heterologous expression of MNPs, it is critical to consider heterologous host selection as well as genetic manipulations for BGCs. In this review, we summarize current progress on the heterologous expression of MNPs as a reference for future research.

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“…Fungal NRPs are synthesised by multimodular NRP synthetase (NRPS) enzymes, using either proteinogenic or non-proteinogenic amino acids to construct the NP (Vassaux et al, 2019).…”

Section: Non-ribosomal Peptides (Nrps)mentioning

confidence: 99%

Recent developments of tools for genome and metabolome studies in basidiomycete fungi and their application to natural product research

2020

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Basidiomycota are a large and diverse phylum of fungi. They can make bioactive metabolites that are used or have inspired the synthesis of antibiotics and agrochemicals. Terpenoids are the most abundant class of natural products encountered in this taxon. Other natural product classes have been described, including polyketides, peptides, and indole alkaloids. The discovery and study of natural products made by basidiomycete fungi has so far been hampered by several factors, which include their slow growth and complex genome architecture. Recent developments of tools for genome and metabolome studies are allowing researchers to more easily tackle the secondary metabolome of basidiomycete fungi. Inexpensive long-read whole-genome sequencing enables the assembly of high-quality genomes, improving the scaffold upon which natural product gene clusters can be predicted. CRISPR/Cas9-based engineering of basidiomycete fungi has been described and will have an important role in linking natural products to their genetic determinants. Platforms for the heterologous expression of basidiomycete genes and gene clusters have been developed, enabling natural product biosynthesis studies. Molecular network analyses and publicly available natural product databases facilitate data dereplication and natural product characterisation. These technological advances combined are prompting a revived interest in natural product discovery from basidiomycete fungi.This article has an associated Future Leader to Watch interview with the first author of the paper.

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Nonribosomal peptides in fungal cell factories: from genome mining to optimized heterologous production

Cited by 28 publications

References 237 publications

GNPS-guided discovery of xylacremolide C and D, evaluation of their putative biosynthetic origin and bioactivity studies of xylacremolide A and B

GNPS-guided discovery of xylacremolide C and D, evaluation of their putative biosynthetic origin and bioactivity studies of xylacremolide A and B

Recent Advances in the Heterologous Expression of Biosynthetic Gene Clusters for Marine Natural Products

Recent developments of tools for genome and metabolome studies in basidiomycete fungi and their application to natural product research

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